Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model
- Park, H., Shim, J.S., Kim, B.S., Jung, H.J., Huh, T.L., Kwon, H.J.
- Biochemical and Biophysical Research Communications 450(1): 561-7 (Journal)
- Registered Authors
- Huh, Tae-Lin
- Adipocyte-derived leucine aminopeptidase (A-LAP), Angiogenesis, Drug screening, Purpurin
- MeSH Terms
- Cell Survival/drug effects
- Cells, Cultured
- Endothelial Cells/drug effects
- Endothelial Cells/physiology*
- Enzyme Inhibitors/pharmacology
- Leucyl Aminopeptidase/antagonists & inhibitors*
- Leucyl Aminopeptidase/metabolism*
- Models, Animal
- Neovascularization, Physiologic/drug effects
- Neovascularization, Physiologic/physiology*
- 24928393 Full text @ Biochem. Biophys. Res. Commun.
Park, H., Shim, J.S., Kim, B.S., Jung, H.J., Huh, T.L., Kwon, H.J. (2014) Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model. Biochemical and Biophysical Research Communications. 450(1):561-7.
Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel member of the M1 family of zinc metallopeptidases, which has been reported to play a crucial role in angiogenesis. In the present study, we conducted a target-based screening of natural products and synthetic chemical libraries using the purified enzyme to search novel inhibitors of A-LAP. Amongst several hits isolated, a natural product purpurin was identified as one of the most potent inhibitors of A-LAP from the screening. In vitro enzymatic analyses demonstrated that purpurin inhibited A-LAP activity in a non-competitive manner with a Ki value of 20 μM. In addition, purpurin showed a strong selectivity toward A-LAP versus another member of M1 family of zinc metallopeptidase, aminopeptidase N (APN). In angiogenesis assays, purpurin inhibited the vascular endothelial growth factor (VEGF)-induced invasion and tube formation of human umbilical vein endothelial cells (HUVEC). Moreover, purpurin inhibited in vivo angiogenesis in zebrafish embryo without toxicity. These data demonstrate that purpurin is a novel specific inhibitor of A-LAP and could be developed as a new anti-angiogenic agent.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes